Ethnic variations in the prevalence of diabetic retinopathy in people with diabetes attending screening in the United Kingdom (DRIVE UK)

Aims

To compare the prevalence of diabetic retinopathy (DR) in people of various ethnic groups with diabetes in the United Kingdom (UK).

Methods

The Diabetic Retinopathy In Various Ethnic groups in UK (DRIVE UK) Study is a cross-sectional study on the ethnic variations of the prevalence of DR and visual impairment in two multi-racial cohorts in the UK. People on the diabetes register in West Yorkshire and South East London who were screened, treated or monitored between April 2008 to July 2009 (London) or August 2009 (West Yorkshire) were included in the study. Data included age, sex, ethnic group, type of diabetes, presenting visual acuity and the results of grading of diabetic retinopathy. Prevalence estimates for the ethnic groups were age-standardised to the white European population for comparison purposes.

Results

Out of 57,144 people on the two diabetic registers, data were available on 50,285 individuals (88.0%), of these 3,323 had type 1 and 46,962 had type 2 diabetes. In type 2 diabetes, the prevalence of any DR was 38.0% (95% confidence interval(CI) 37.4% to 38.5%) in white Europeans compared to 52.4% (51.2% to 53.6%) in African/Afro-Caribbeans and 42.3% (40.3% to 44.2%) in South Asians. Similarly, sight threatening DR was also significantly more prevalent in Afro-Caribbeans (11.5%, 95% CI 10.7% to 12.3%) and South Asians (10.3%, 9.0% to 11.5%) compared to white Europeans (5.5%, 5.3% to 5.8%). Differences observed in Type 1 diabetes did not achieve conventional levels of statistical significance, but there were lower numbers for these analyses.

Conclusions

Minority ethnic communities with type 2 diabetes in the UK are more prone to diabetic retinopathy, including sight-threatening retinopathy and maculopathy compared to white Europeans.     

Identification of KIF3A as a novel candidate gene for childhood asthma using RNA expression and population allelic frequencies differences

Background

Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes.

Methodology/Principal Findings

Using epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p<0.05) in our discovery cohort and in three independent cohorts at either the SNP or gene level (p<0.05). Further, we determined that our selection approach was superior to random selection of genes either differentially expressed in asthmatics compared to controls (p = 0.0049) or selected based on the literature alone (p = 0.0049), substantiating the validity of our gene selection approach. Importantly, we observed that 7 of 9 SNPs in the KIF3A gene more than doubled the odds of asthma (OR = 2.3, p<0.0001) and increased the odds of allergic disease (OR = 1.8, p<0.008). Our data indicate that KIF3A rs7737031 (T-allele) has an asthma population attributable risk of 18.5%. The association between KIF3A rs7737031 and asthma was validated in 3 independent populations, further substantiating the validity of our gene selection approach.

Conclusions/Significance

Our study demonstrates that KIF3A, a member of the kinesin superfamily of microtubule associated motors that are important in the transport of protein complexes within cilia, is a novel candidate gene for childhood asthma. Polymorphisms in KIF3A may in part be responsible for poor mucus and/or allergen clearance from the airways. Furthermore, our study provides a promising framework for the identification and evaluation of novel candidate susceptibility genes.     

Structural and Functional Measures of Efficacy in Response to Bevacizumab Monotherapy in Diabetic Macular Oedema: Exploratory Analyses of the BOLT Study (Report 4)

Background

To describe structural and functional changes associated with diabetic macular oedema (DMO) treated with intravitreal bevacizumab over 24 months.

Methods

A post-hoc analysis of the data of 34 patients that completed 24 months follow-up in the intravitreal bevacizumab arm of a prospective, randomized controlled trial (BOLT study) was performed. The outcome measures previously used in clinical trials of intravitreal ranibizumab in DMO were employed to describe the visual acuity and macular thickness changes at 12 and 24 months.

Results

The standard outcomes of mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) in participants treated with bevacizumab were comparable to those reported in association with ranibizumab. However, exploratory analyses showed that thick maculae at baseline defined as CMT of ≥400 µm, remained significantly thicker than those <400 µm with intensive bevacizumab therapy, despite a comparable gain in visual acuity at both 12 and 24 months. The proportion of subjects that attained a dry macula doubled in both CMT groups between the 12 and 24-month time-points.

Conclusions

These findings provide valuable information both for clinical practice and trials. Further studies are required to investigate the impact of intravitreal bevacizumab on retinal thickness profiles in DMO.     

Book Review

To study the variability and to identify the species of Begomovirus associated with yellow mosaic disease of blackgram in Andhra Pradesh, India, infected blackgram samples were collected from six districts belonging to three regions of Andhra Pradesh. The total DNA was isolated by modified CTAB method and amplified with coat protein gene-specific primers (RHA-F and AC abut) resulting in 900?bp gene product. The PCR products were cloned, sequenced and deposited in GenBank. The sequence analysis of six clones showed that the size of amplified CP gene of YMV was 920?bp. Based on nucleotide sequence identity of six isolates representing three regions of Andhra Pradesh, the isolates from Rayalaseema and Telangana region are the same variant of YMV (>99.5% identity) and isolate from coastal Andhra is another variant of YMV (>95.4%) when compared with other region isolates. Comparison of CP gene sequence of YMV-TPT isolate with 27 other isolates in database revealed more than 93.2 and 86.2% identity with MYMIV isolates and less than 80 and 64% identity with MYMY isolates that originate from Indian sub-continent and South-East Asia at nucleotide and amino acid level, respectively. Phylogenetic tree based on CP gene sequences of six isolates with other isolates from GenBank formed unique cluster with MYMIV. Hence the YMV infecting blackgram in Andhra Pradesh is caused by MYMIV rather than MYMY as reported in Tamil Nadu which is adjoining state in southern India.     

Exploring hydrogen bond in the excited state leading toward intramolecular proton transfer: detailed analysis of the structure and charge density topology along the reaction path using QTAIM

Excited state intramolecular proton transfer (ESIPT) reaction along the O-H[Symbol: see text][Symbol: see text][Symbol: see text][Symbol: see text]O hydrogen bond of o-hydroxy benzaldehyde (OHBA), methyl salicylate (MS) and salicylic acid (SA) was investigated by ab-initio quantum chemical calculation and theory of atoms and molecules (QTAIM) for the first time. Variation in several geometric as well as QTAIM parameters along the reaction coordinate was monitored in the fully relaxed excited state potential energy curve (PEC) obtained from intrinsic reaction coordinate (IRC) analysis. Although, the excited state barrier height for the forward reaction (?E (0) (#) ) reduces substantially in all the systems, MS and SA do not show any obvious asymmetry for proton transfer. For MS and SA, the crossover of the bond index as well as the lengths of the participating bonds at the saddle point is assigned due to this symmetry in accordance with bond energy - bond order (BEBO) model, which does not hold true in OHBA both in the ground and excited states. Bond ellipticity, covalent and metallic character were examined for different structures along the reaction path within the QTAIM framework. The QTAIM analysis was found to be able to uniquely distinguish between the ground and excited states of the OHBA molecule as well as both determining the effects on the bonding character of adding different substituent groups and differentiating between the ESIPT reactions in the SA and MS molecules.     

Family Practices' Achievement of Diabetes Quality of Care Targets and Risk of Screen-Detected Diabetic Retinopathy

Background

We aimed to determine whether family practices'' achievement of diabetes quality of care targets is associated with diabetic retinal disease in registered patients.

Methods

Data for achievement of diabetes quality of care targets, including the proportion of patients with HbA1c≤7.5%, for 144 family practices in London UK, for the years 2004/5 to 2007/8, were linked to data from a population-based diabetes eye screening programme collected from September 2007 to February 2009. Analyses were adjusted for age, sex, duration and type of diabetes, unadjusted diabetes prevalence, ethnicity and deprivation category.

Results

Data were analysed for 24,458 participants with one or more eye screening results in the period. There were 9,332 (38%) with any diabetic retinopathy and 2,819 (11.5%) with sight threatening diabetic retinopathy (STDR), including 2,654 (10.9%) with maculopathy. Among participants registered at 13 family practices that were in the highest quartile for achievement of the HbA1c quality of care target for all four years of study, the relative odds of any diabetic retinopathy were 0.78 (0.69 to 0.88) P<0.001. For participants at 12 practices consistently in the lowest quartile of HbA1c achievement, the relative odds of any diabetic retinopathy were 1.16 (1.03 to 1.30), P = 0.015. In the highest achieving practices, the relative odds of maculopathy were 0.74 (0.62 to 0.89), P = 0.001 and STDR 0.77 (0.65 to 0.92), P = 0.004.

Conclusions

The risk of diabetic retinopathy might be lower at family practices that consistently achieve highly on diabetes quality of care targets for HbA1c.     

Fluorimetric studies on the binding of 4-(dimethylamino)cinnamic acid with micelles and bovine serum albumin

The constrained photophysics of intramolecular charge transfer (ICT) probe 4-(dimethylamino)cinnamic acid (DMACA) was studied in different surfactant systems as well as in presence of model water soluble protein bovine serum albumin (BSA). Binding of the probe in ionic micelles like sodium dodecyl sulfate (SDS) and cetyl trimethyl ammonium bromide (CTAB) causes an increase in ICT fluorescence intensity, whereas, in non-ionic TritonX-100 (TX-100) the intensity decreases with a concomitant increase in emission from locally excited (LE) state. The observations were explained in terms of the different binding affinity, location of the probe and also the nature of specific hydrogen bonding interaction in the excited state nonradiative relaxation process of DMACA. The ICT fluorescence emission yield decreases in BSA due to the locking in of the probe buried in the hydrophobic pocket of the protein structure. SDS induced uncoiling of protein and massive cooperative binding between BSA and SDS is manifested by the release of probe molecules in relatively free aqueous environment.     

Fluorescence studies on the photophysical properties and encapsulation behavior of acetaminophen in different environments

A systematic study on the spectroscopy and photophysical properties of widely used analgesic and anti-pyretic drug acetaminophen (NAPAP) was presented using steady state and time-resolved fluorescence spectroscopy. The results in homogeneous solvents were compared with those in bio-mimicking environments of cyclodextrin and micellar cavities. Extensive theoretical calculations using time dependent density functional theory (TDDFT) were also done to substantiate the spectral assignment as well as to compare the structure and stability of possible hydrogen bonded conformations of NAPAP in aqueous medium. Facile proton dissociation occurs due to extensive charge redistribution in the excited state. The variation in fluorescence yield and the life time of excited state species in cyclodextrin cavities and micellar medium is due to shift in acid-base dissociation equilibrium in these environments.     

Protein kinase C-ε protects MCF-7 cells from TNF-mediated cell death by inhibiting Bax translocation

We have previously shown that protein kinase Cε (PKCε) acts as an antiapoptotic protein and protects breast cancer MCF-7 cells from tumor necrosis factor-α (TNF)-mediated apoptosis. In the present study, we have investigated the mechanism by which PKCε inhibits TNF-induced cell death. Overexpression of wild-type PKCε (WT-PKCε) in MCF-7 cells decreased TNF-induced mitochondrial depolarization. Depletion of Bax by small interfering RNA (siRNA) attenuated TNF-induced cell death. Overexpression of PKCε in MCF-7 cells decreased dimerization of Bax and its translocation to the mitochondria. Knockdown of PKCε using siRNA induced Bax dimerization and mitochondrial translocation. PKCε was coimmunoprecipitated with Bax in MCF-7 cells. These results suggest that PKCε mediates its antiapoptotic effect partly by preventing activation and translocation of Bax to the mitochondria.